Delayed onset and decreased severity of experimental autoimmune uveoretinitis in mice lacking nitric oxide synthase type 2

J Neuroimmunol. 2000 Oct 2;110(1-2):31-44. doi: 10.1016/s0165-5728(00)00313-1.

Abstract

To investigate the role of nitric oxide (NO), produced by the inducible form of NO synthase (NOS-2) in the development of experimental autoimmune uveoretinitis (EAU), we immunized C57BL/6x129Sv (H-2(b)) mice carrying a targeted disruption of the gene encoding NOS-2 (NOS-2[-/-]), and wild-type (WT) C57BL/6x129Sv controls with interphotoreceptor retinoid binding protein (IRBP). NOS-2[-/-] mice developed a clinical EAU with delayed onset and decreased severity compared to WT controls. The ocular tissues from WT mice contained activated F4/80 macrophages with NOS-2 expression and retinal destruction whereas less intense EAU was detected in NOS-2[-/-] mice. The expression of NOS-2 mRNA was detected in the retina at the peak of EAU in WT. Analysis of cytokine production in the spleen from NOS-2[-/-] mice by RT-PCR showed high levels of IL-10 mRNA. Our results demonstrate that NO is clearly involved in EAU and may be important for the regulation of immune responses through the regulation of IL-10.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Cell Division
  • Concanavalin A / pharmacology
  • Eye Proteins*
  • Female
  • Gene Expression Regulation, Enzymologic / immunology
  • Immunization
  • Immunoglobulin G / blood
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Lymphocytes / cytology
  • Lymphocytes / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type II
  • RNA, Messenger / analysis
  • Retina / enzymology
  • Retina / immunology
  • Retinitis / immunology*
  • Retinitis / metabolism*
  • Retinol-Binding Proteins / immunology
  • Retinol-Binding Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severity of Illness Index
  • Spleen / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Uveitis / immunology*
  • Uveitis / metabolism*

Substances

  • Eye Proteins
  • Immunoglobulin G
  • RNA, Messenger
  • Retinol-Binding Proteins
  • Tumor Necrosis Factor-alpha
  • interstitial retinol-binding protein
  • Concanavalin A
  • Interleukin-10
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse